The goal of this research project is the continued development of a family of novel nanofabricated particles for use as carriers to deliver a variety of different types of bioactive molecules (DNA, RNA, proteins, peptides) and nanoparticle sensors via particle acceleration methods. The particles are fabricated using the controlled assembly of nanoparticles, polymers and biomolecules via a layer-by-layer technique where the core and subsequent layer each add specific functionality to the final particle. These nanocomposite particles will increase the efficiency and reliability of the currently used biolistic process, and enable novel biolistic delivery applications. These include the delivery of RNAi, antisense oligonucleotides, peptides, and sensors to living cells and tissues for a variety of life science research applications, and for human therapeutic interventions. The key technical objectives to be achieved include the development of manufacturing and process development steps for the production of nanofabricated particles, the documented demonstration of the enhanced efficacy of these particles in a variety of model system applications, and synthesis and characterization of a family of chemically distinct particles with specific functionality. The ability to deliver nucleic acids and polypeptides to cells and tissues of interest is one of the fundamental and required technical achievements that has, in part, been at the foundation of molecular biology, gene therapy and related fields. Particle acceleration methods, also referred to as biolistic delivery, is one of several delivery methods in routine use. Improvements to any of these delivery methods is of relevance to human health because the delivery of nucleic acids, such as DNA, is frequently an essential step in the research and development of medical diseases. The nanofabricated carrier particles we will develop will significantly improve the efficacy of the biolistic delivery process and enable its use in novel applications where currently there is an unmet need. [unreadable] [unreadable] [unreadable] [unreadable]